The long-term goal of the projects is to identify the rules that govern the cellular interactions between afferent axons and their target cells under the changing conditions of neurogenesis, maturation, aging, and sensory deprivation resulting from deafferentation. The interactions between the PNS and the CNS that affect synapse formation between sensory neurons will be focused on, as studied in the chick vestibular system. One class of vestibular ganglion cells and their target cells, in the tangential vestibular nucleus and in the vestibular epithelium, will be studied. These ganglion cells produce colossal vestibular fibers which form spoon endings on the principal cells of the tangential nucleus and calyces with the type I and type II hair cells in the vestibular epithelium. In the preceding project, the normal synaptic interactions of the spoon endings and the calycine endings were quantified in embryos, hatchlings, and young adult chickens using ultrastructural techniques. These findings provide a basis to evaluate future projects on what happens to the same target neurons deprived of vestibular inputs in embryos and hatchlings. Moreover, the previous findings have generated a need to expand the scope of the proposal to include ultrastructural studies of the spoon endings in aging animals, to employ the freeze-fracture technique for the study of gap junction at the spoon endings, to study early synaptogenesis in the vestibular epithelium, to determine the synaptic arrangements of vestibular type II hair cells, to replace the otocyst with an optic cup in chick embryos, and to use horseradish peroxidase and tritiated amino acids for tracing the afferent and efferent connections of the tangential nucleus. The work has both clinical and basic science relevance. When animals undergo deafferentation, the response of the target neurons is variable, depending in part on age. Knowledge of the rules that govern the formation of synaptic organization and its reorganization should be useful in future studies concerned with the prevention or treatment of various conditions that cause failure in normal processing of vestibular information, or sensory information in general. Structural analysis of the development of synaptic connections in the vestibular pathways should lead to a greater appreciation of the development of the neural coding mechanism and the role of afferent fibers on the development of neural networks.